This review describes the self-assembly of sparsely grafted amphiphilic copolymers and highlights the effects of structural factors and solvents on their self-assembly behaviour.

The aggregation of a dipeptide, L-leucine-glycine (Leu−Gly), at 100 mmol dm −3 has been observed in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)−water and 2-propanol (2-PrOH)−water solvents at various alcohol mole fractions, x A , using the dynamic light scattering technique and molecular dynamics (MD) simulations. Leu−Gly was dissolved into the HFIP solvents at the concentration over the entire x A range, while the dipeptide was not dissolved in the 2-PrOH solvents above x A = 0.6. Interestingly, the MD snapshots showed different shapes of Leu−Gly aggregates in the HFIP and 2-PrOH solvents. A linear-shaped aggregate forms in the former; in contrast, a spherical-shaped aggregate is generated in the latter. The solvation structure of each moiety of Leu−Gly in the HFIP and 2-PrOH solvents was observed using experimental and theoretical techniques, 1 H and 13 C NMR, IR, and 19 F− 1 H HOESY measurements and MD simulations. These results gave us the reasons for the different shapes of Leu−Gly aggregates in both solvents. In the HFIP solvents, most of the moieties of the dipeptide are easily solvated by HFIP. This induces the elongated structure of Leu−Gly, leading to the electrostatic interaction between the N-(NH 3 + group) and C-(COO − group) terminals of dipeptide molecules. On the other hand, in the 2-PrOH solvents, water molecules that initially solvate the moieties of Leu−Gly, such as the N-and C-terminals and the peptide linkage, are not easily eliminated even as the x A is close to 0.6. The water molecules can bridge such moieties of Leu−Gly to form spherical-shaped aggregates. The diffusion coefficients of Leu−Gly in both alcohol−water binary solvents were experimentally determined by NMR DOSY to estimate the geometries of the aggregates in the solvents. The sizes of Leu−Gly aggregates obtained by DOSY for both solvent systems were consistent with those estimated from the MD snapshots.

Transplantable catalytic reactors have attracted considerable attention as therapeutic biomedical materials. However, existing transplantable reactors such as biocatalytic films are limited by their invasiveness. Here, we report the fabrication of biocatalytic supramolecular hydrogels via self-assembly of amphiphilic glycopeptides. We show that the hydrogels have shear-thinning properties, demonstrating their potential to be administered using a syringe. Enzymes can be loaded into the hydrogels by simply adding enzyme solution, and the enzyme-loaded hydrogels can transform a prodrug into an anticancer drug that inhibits tumor cell growth. This study demonstrates the potential of these biocatalytic hydrogels as injectable therapeutic reactors for enzyme prodrug therapy.